Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder. Its incidence has been reported to be 0.6-2.6/100,000 (Roman, J Neurol Neurosurg Psychiatry. 1996. 61 (2):131-7) with a slight male predominance. The disease incidence peaks in the sixth decade of life (Nelson, Clin. Neurosci. 3, 327 (1995)); survival is typically 2 to 5 years. ALS inevitably leads to death from respiratory paralysis in the absence of mechanical ventilation. Familial cases account for about 10% of ALS; mutations in cytosolic copper-zinc superoxide dismutase 1 (SOD1) have been shown to account for 20-25% of these familial cases (Rosen, Nature 364, 362 (1993)). Mutations in vesicle-associated membrane protein-associated protein (VAPB) have been shown to cause either classical ALS or atypical motor neuron disease in a small number of Brazilian families. A handful of other genes have been implicated in atypical motor neuron disease, including upper-motor-neuron-predominant ALS2 (alsin), juvenile ALS (senataxin), and lower motor neuropathy (DCTN1). A second form of juvenile inherited ALS (recessive in this case) has been linked to chromosome 15q (Hentati et al., Neurogenetics 2, 55 (1998)). In the majority of familial classical ALS cases, however, the causative gene is unknown. High-penetrance classical ALS pedigrees have been reported with linkage to chromosomes 16, and 18, while families with ALS with and without frontotemporal dementia have been reported with linkage to chromosome 9.